Effects of PEGylated paclitaxel nanocrystals on breast cancer and its lung metastasis

Abstract

As an attractive strategy developed rapidly in recent years, nanocrystals are used to deliver insoluble drugs. PEGylation may further prolong the circulation time of nanoparticles and improve the therapeutic outcome of drugs. In this study, paclitaxel (PTX) nanocrystals (PTX-NCs) and PEGylated PTX nanocrystals (PEG-PTX-NCs) were prepared using antisolvent precipitation augmented by probe sonication. The characteristics and antitumor efficacy of nanocrystals were investigated. The results indicated that the nanocrystals showed rod-like morphology, and the average particle size was 240 nm and 330 nm for PTX-NCs and PEG-PTX-NCs, respectively. The PEG molecules covered the surface of nanocrystals with an 11.54 nm fixed aqueous layer thickness (FALT), much higher than that of PTX-NCs (0.2 nm). PEG-PTX-NCs showed higher stability than PTX-NCs under both storage and physiological conditions. In breast cancer xenografted mice, PEG-PTX-NCs showed significantly better tumor inhibition compared to saline (p < 0.001) and PTX-NC groups (p < 0.05) after intravenous administration. In a model of lung tumor metastasis quantified by the luciferase activity, the PEG-PTX-NCs group showed higher anticancer efficacy not only than saline and PTX-NCs groups, but also than Taxol®, achieving an 82% reduction at the end of the experiment. These studies suggested the potential advantages of PEGylated PTX nanocrystals as alternative drug delivery systems for anticancer therapy.

A Comparative In Vivo Study of Albumin‐Coated Paclitaxel Nanocrystals and Abraxane

“…In addition, NC systems reported so far have not shown an improved antitumor efficacy as compared to commercial PTX formulations at the equivalent dose . PTX NCs stabilized with Pluronic polymers were not significantly better than Taxol in delaying tumor growth .…”

“…When transferrin (Tf)‐coated PTX NCs were used to treat Tf‐receptor‐expressing KB tumors, their performance was better than bare NCs (tumor growth suppression rate 45.1% vs 28.8%) but not superior to Taxol's (tumor growth suppression rate 93.3%). PTX NCs coated with PEG via covalent conjugation improved the stability of surface protection, but their anticancer efficacy was not significantly better than those of Abraxane and Taxol . In most cases, the main advantage of NC systems was limited to eliminating the use of toxic solubilizers rather than improving the therapeutic efficacy of unit dose.…”

Nanoparticles for imaging and treatment of metastatic breast cancer

“…In a model of lung tumor metastasis quantified by the luciferase activity, the PEG-PTX nanocrystals showed higher anticancer efficacy than PTX alone, achieving an 82% reduction of tumor growth . [49] In contrast to the large size of these NPs, another research group has developed PTX nanodots with much smaller size (~10 nm) through a droplet-confined/cryodesiccation-driven crystallization approach. The iRGD grafted PTX nanodots showed intratumoral penetration and reached cancer stem cells that reside in the tumor core.…”

Albumin-coated nanocrystals for carrier-free delivery of paclitaxel

“…Another type of PTX NC were produced by transforming an amorphous mixture of PTX and Pluronic F127 into crystalline particles and tested in two tumor models [13]. As NC were mostly distributed in the MPS organs leaving little drug in circulation [12, 14, 15], the NC were further modified with polyethylene glycol (PEG) by forming NC together with PEGylated PTX [16] or a crosslinkable polymeric amphiphile containing PEG [17]. Recently, iron-tannic acid complex was used to coat PTX nanoassemblies with an intention to reduce their MPS uptake [18].…”